Saratov JOURNAL of Medical and Scientific Research

COVID-19 associated myocarditis: mechanisms of pathogenesis, problems of diagnostics (review)

Year: 2021, volume 17 Issue: №3 Pages: 571-577
Heading: Тhematic supplement Article type: Review
Authors: Sergeeva V.A., Lipatova Т.Е.
Organization: Saratov State Medical University

The review summarizes actual information on inflammatory myocardial injury in COVID-19. The most update works from 2020-2021 were used as the literature sources, as well as earlier research containing fundamental information on the relevant topic. The substantial information is reflected in the review. Used queries: myocarditis, myocardial injury, COVID-19 — in the search engines PubMed/MedLine, eLibrary. The analysis of current international literature has demonstrated convincing evidence of the possible development of myocarditis in case of new coronavirus infection. The histological verification of myocardial injury associated with COVID-19 presents significant difficulties, since in conditions of a severe course of infection; it is not always possible to perform endomyocardial biopsy. In this regard, the statistics do not reflect complete information on the prevalence of COVID-19 associated myocarditis. All mechanisms of the pathogenesis of inflammatory myocardial injury have not been completely clarified. Due to the ambiguity of the prognosis of patients with COVID-19 associated myocarditis, further study of the problem is required.

1. Dominguez F, Kuhl U, Pieske B, et al. Update on myocarditis and inflammatory cardiomyopathy: reemergence of endomyocardial biopsy. Rev Esp Cardiol 2016; 69: 178-87.
2. Trachtenberg BH, Hare JM. Inflammatory cardiomyopathic syndromes. Circ Res 2017; 121: 803-18.
3. Caforio AL, Pankuweit S, Arbustini, et al. Current state of knowledge on etiology, diagnosis, management, and therapy of myocarditis: A position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J 2013; 34: 2636-48. URL: /10.1093/eurheartj/eht210
4. Official website of the Russian Society of Cardiology. URL: rekom_Miokardit. pdf
5. Xiong TY, Redwood S, Prendergast B, Chen M. Coronaviruses and the cardiovascular system: acute and longterm implications. Eur Heart J 2020; 0: 1-3. URL: https://
6. Chen L, Li X, Chen M, et al. The ACE2 expression in human heart indicates new potential mechanism of heart injury among patients infected with SARS-CoV-2. Cardiovasc Res 2020; 116: 1097-100.
7. Jafarzadeh A, Chauhan P, Saha B, et al. Contribution of monocytes and macrophages to the local tissue inflammation and cytokine storm in COVID-19: Lessons from SARS and MERS, and potential therapeutic interventions. Life Sci 2020; 257: 118-102. URL: https://doi.Org/10.1016/j. Ifs. 2020.118102
8. Sergienko IV, Rezinkina PK. New coronavirus infection COVID-19 and cardiovascular diseases. Features of therapy. The Journal of Atherosclerosis and Dyslipidemias 2021; 2 (43): 5-23.
9. Sardu С, Gambardella J, Morelli MB, et al. Hypertension, thrombosis, kidney failure, and diabetes: Is COVID-19 an endothelial disease? A comprehensive evaluation of clinical and basic evidence. J Clin Med 2020; 9 (5): 1417. DOI: 10.3390/jcm9051417.
10. Verdecchia P, Cavallini C, Spanevello A, Angeli F. The pivotal link between ACE2 deficiency and SARS-CoV-2 infection. Eur J Intern Med 2020; 76: 14-20. DOI: 10.1016/j. ejim. 2020.04.037.
11. Lazzerini PE, Boutjdir M, Capecchi PL. COVID-19, arrhythmic risk and inflammation: mind the gap. Circulation 2020; 142(1): 7-9. DOI: 10.1161/CIRCULATIONAHA. 120.047293.
12. Zheng YY, Ma YT, Zhang JY, Xie X. COVID-19 and the cardiovascular system. Nature Reviews Cardiology 2020; 17 (5): 259-60.
13. Cortegiani A, Ingoglia G, Ippolito M, et al. A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19. J Crit Care 2020; 57: 279-83. DOI: 10.1016/j. jcrc. 2020.03.005.
14. Chinello P, Petrosillo N, Pittalis S, et al. QTc interval prolongation during favipiravir therapy in an Ebolavirus-infected patient. PLoS Negl Trop Dis 2017; 11 (12): e0006034. DOI: 10.1371/journal. pntd. 0006034.
15. Su S, Wong G, Shi W, et al. Epidemiology, genetic recombination and pathogenesis of coronaviruses. Trends Microbiol 2016; 24: 490-502.
16. Alhogbani T. Acute myocarditis associated with novel Middle East respiratory syndrome coronavirus. Ann Saudi Med 2016;36:78-80.
17. Tavazzi G, Pellegrini C, Maurelli M, et al. Myocardial localization of coronavirus in COVID-19 cardiogenic shock. Eur J Heart Fail 2020; 22 (5): 911-5. DOI: 10.1002/ejhf. 1828.
18. Basso C, Leone O, Rizzo S, et al. Pathological features of COVID-19 associated myocardial injury: a multicentre cardiovascular pathology study. Eur Heart J 2020; 41: 3827-35.
19. Dolhnikoff M, Ferreira Ferranti J, de Almeida Monteiro RA, et al. SARS-CoV-2 in cardiac tissue of a child with COVID-19-related multisystem inflammatory syndrome [published correction appears in Lancet Child Adolesc Health 2020 Oct; 4 (10): e39]. Lancet Child Adolesc Health 2020; 4 (10): 790-94. DOI: 10.1016/S2352-4642 (20) 30257-1.
20. Ruan Q, Yang K, Wang W, et al. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan. Intensive Care Med 2020; 46: 846-48.
21. Kogan EA, Berezovskiy YuS, Blagova OV, et al. Miocarditis in patients with COVID-19 confirmed by immunohistochemical. Cardiology 2020; 60 (7): 4-10.
22. Escher F, Pietsch Н, Aleshcheva G, et al. Detection of viral SARS-CoV-2 genomes and histopathological changes in endomyocardial biopsies. ESC Heart Fail 2020; 7 (5): 2440-7. DOI: 10.1002/ehf2.12805.
23. Lindner D, Fitzek A, Brauninger H, et al. Association of Cardiac Infection with SARS-CoV-2 in Confirmed COVID-19 Autopsy Cases. JAMA Cardiol 2020; 5 (11): 1281-5. DOI: 10.1001/jamacardio. 2020.3551.
24. Craver R, Huber S, Sandomirsky M, et al. Fatal Eosinophilic Myocarditis in a Healthy 17-Year-Old Male with Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2c). Fetal and Pediatric Pathology 2020; 39 (3): 263-8. [Epubahead of print]. DOI: 10.1080/15513815.2020.1761491.
25. Huang C, Wang Y, Li X, et. al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet 2020; 395 (10223): 497-506. DOI: http://doi.Org/10.1016/s0140-6736(20)30183-5.
26. Fu Y, Cheng Y, Wu Y Understanding SARS-CoV-2-mediated inflammatory responses: from mechanisms to potential therapeutic tools. Virol Sin 2020; 35 (3): 266-71.
27. Liu B, Li M, Zhou Z, et al. Can we use interleukin-6 (IL-6) blockade for coronavirus disease 2019 (COVID-19) — induced cytokine release syndrome (CRS). J Autoimmun 2020; 111: 102452. URL: https://doi.Org/10.1016/j.jaut. 2020.102452.
28. Tajbakhsh A, Hayat SMG, et al. COVID-19 and cardiac injury: clinical manifestations, biomarkers, mechanisms, diagnosis, treatment, and follow up. Expert Review of Anti-infective Therapy 2021; 19 (3): 345-57. DOI: 10.1080/14787210 .2020.1822737.
29. Wenzhong L, Hualan L. COVID-19: Attacks the 1-Beta Chain of Hemoglobin and Captures the Porphyrin to Inhibit Human Heme Metabolism. Available at: URL: https:// Accessed 2021 Oct 14.
30. Ramos SG, Rattis B, Ottaviani G, et al. ACE2 Down-Regulation May Act as a Transient Molecular Disease Causing RAAS Dysregulation and Tissue Damage in the Microcirculatory Environment Among COVID-19 Patients. Am J Pathol2021; 191: 1154-64. DOI: 10.1016/j. ajpath. 2021.04.010.
31. Driggin E, Madhavan MV, Bikdeli В et al. Cardiovascular considerations for patients, health care workers, and health systems during the COVID-19 pandemic. J Am Coll Cardiol 2020; 75 (18): 2352-71. DOI: 10.1016/j. jacc. 2020.03.031.
32. Hendren NS, Drazner MH, Bozkurt B, et al. Description and proposed management of the acute COVID-19 cardiovascular syndrome. Circulation 2020; 141 (23): 1903-14. DOI: 10.1161/CIRCULATIONAHA. 120.047349.
33. Kawakami R, Sakamoto A, Kawai K, et al. Pathological evidence for SARS-CoV-2 as a cause of myocarditis: JACC Review Topic of the Week. J Am Coll Cardiol 2021; 77 (3): 314-25.
34. Long B, Brady WJ, Koyfman A, et al. Cardiovascular complications in COVID-19. Am J Emerg Med 2020 Jul; 38 (7): 1504-7. DOI: 10.1016/j. ajem. 2020.04.048.
35. Sawalha K, Abozenah M, Kadado AJ, et al. Systematic Review of COVID-19 Related Myocarditis: Insights on Management and Outcome. Cardiovasc Revasc Med 2021 Feb; 23: 107-13. DOI: 10.1016/j. carrev. 2020.08.028.
36. Doyen D, Moceri P, DucreuxD, Dellamonica J. Myocarditis in a patient with COVID-19: a cause of raised troponin and ECG changes. Lancet 2020; 395 (10235): 1516. DOI: 10.1016/S0140-6736 (20) 30912-0.
37. D'Andrea A, Di Giannuario G, Marrazzo G, et al. The role of multimodality imaging in COVID-19 patients: from diagnosis to clinical monitoring and prognosis. G Ital Cardiol 2021; 21: 345-53.
38. EspositoA, PalmisanoA, Natale Letal. Cardiac magnetic resonance characterization of myocarditis-like acute cardiac syndrome in COVID-19. JACC Cardiovasc Imaging 2020; 13: 2462-5.
39. Wang D, Ни В, Ни C, et. al. Clinical Characteristics of 138 Hospitalized Patients with 2019 Novel Coronavirus Infected Pneumonia in Wuhan, China. JAMA 2020; 323 (11): 1061. DOI:
40. Yang X, Yu Y, Xu J, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med 2020; 8 (5): 475-81.
41. GuoT, FanY, Chen M, etal. Association of cardiovascular disease and myocardial injury with outcomes of patients hospitalized with 2019-coronavirus disease (COVID-19). JAMA Cardiol 2020; 5 (7): 811-8.
42. Deng P, Ke Z, Ying B, et al. The diagnostic and prognostic role of myocardial injury biomarkers in hospitalized patients with COVID-19. Clin Chim Acta 2020; 510: 186-90.
43. Zinellu A, Sotgia S, Fois AG, et al. Serum CK-MB, COVID-19 severity and mortality: An updated systematic review and meta-analysis with meta-regression. Advances in Medical Sciences 2021; 66 (2): 304-14. DOI: https://doi.Org/10.1016/j. advms. 2021.07.001.
44. Official website of the Russian Society of Cardiology. URL: rekom_HSN. pdf
45. Caro-Codon J, Rey JR, Buno A et al. Characterization of NT-proBNP in a large cohort of COVID-19 patients. Eur J Heart Fail 2021; 23: 456-64. URL: 2095
46. Practice of echocardiography during the COVID-19 pandemic: guidance from the Canadian Society of Echocardiography. [Internet] 2020: 1-4. URL: pdf. Accessed Oct 8, 2021.
47. Pirzada A, Mokhtar AT, Moeller AD. COVID-19 and Myocarditis: What Do We Know So Far? CJC Open 2020 May 28; 2 (4): 278-85. DOI: 10.1016/j. cjco. 2020.05.005.
48. Konopleva YuYu, Petrova EV Heart Damage with COVID-19 (Clinical Observations). Radiology — Practice 2020; 6 (84): 61-7.
49. Goha A, Mezue К, Edwards Р, et al. COVID-19 and the heart: An update for clinicians. Clin Cardiol 2020; 43 (11): 1216-22. DOI: 10.1002/clc. 23406.

2021_03-1_571-577.pdf418.97 KB

No votes yet